Three new seco-ursadiene triterpenoids from Salvia syriaca

Three new seco-ursadiene triterpenoids 1–3 together with 11 known compounds were isolated from Salvia syriaca of Jordanian origin. The compounds were identified by using NMR spectroscopy including extensive 2D NMR experiments and mass spectrometry. The structure of compound 3 was confirmed by X-ray crystallography, and the information thus obtained was used to confirm the stereochemistry of compounds 1 and 2. This is the second report of 17,22-seco-17(28),12-ursadien-22-oic acids.     

Antibacterial and antioxidant properties of phyto-synthesized silver nanoparticles using Lavandula stoechas extract

Due to environmentally friendly and cost- effective issues, biological methods for silver nanoparticles (AgNPs) synthesis are advantageous over chemical and physical ones. In this study, AgNPs synthesized using Lavandula stoechas extract as a reductant and its antioxidant capacity, antibacterial property and cytotoxicity effect were investigated. The phyto-synthesized AgNPs were characterized using various analyses such as transmission electron microscopy (TEM), scanning electron microscopy (SEM), x-ray diffraction (XRD) as well as Fourier transform infrared (FT-IR). The prepared nanoparticles were spherical on shape with the size about 20–50 nm. Antibacterial studies through agar disk diffusion method confirmed the antibacterial potential of phyto-synthesized AgNPs toward two clinical Staphylococus aureus and Pseudomonas aeruginosa bacteria, although MTT assay demonstrated that S. aureus (MIC = 125 μg/ml) was more susceptible to AgNPs than P. aeruginosa (MIC = 250 μg/ml). Moreover, the cytotoxicity assay of phyto-synthezied AgNPs showed a low cytotoxic effect on RAW264 cell line at 62.5 μg/ml as an effective concentration. Also the considerable antioxidant capacity of the AgNPs confirmed through DPPH assay. Great antibacterial and antioxidant properties along with biocompatibility make the suggested phyto-synthesized AgNPs a great candidate for different biomedical applications including wound healing.     

2-[(4-Aminobutyl)ferrocenylmethylidene]-5,6-dimethoxy-1-indanone derivatives: Synthesis,characterization, and investigation of electro-optical properties

A ferrocenyl-based, chromophore-containing 1-indanone derivative was synthesized through crotonic condensation between 4-chlorobutylferrocenecarboxaldehyde and 5,6-dimethoxy-1-indanone followed by the nucleophilic substitution of chlorine atom of the obtained dyad with different aromatic and aliphatic amines. The electrochemical and optical properties of the synthesized compounds were investigated to explore the relationship between their structures and optical and electrochemical properties. The bandgaps determined from optical absorption spectra ranged from 2.05 to 2.15 eV. The important electrochemical parameters, including the peak potential separation, peak current ratios, and the dependence of peak currents on the scan rate, were studied. Results showed an electrochemically reversible redox system with diffusion-controlled redox process for the synthesized compounds. The study of quantum chemistry was performed on the synthesized compounds using the density functional theory approach. The B3LYP method and 6-311 G(d) basis set were used for optimizing the structures in the gas phase. The theoretical and experimental results show that these compounds can be considered as candidates to be used in optical applications.     

Zirconium oxide complex anchored on boehmite nanoparticles as highly reusable organometallic catalyst for C–S and C–O coupling reactions

Boehmite nanoparticles were prepared by a simple and inexpensive procedure in water using commercially available materials without inert atmosphere. Then, the surface of the boehmite nanoparticles was modified using 3‐mercaptopropyltrimethoxysilane and subsequently zirconium oxide was supported on the modified surface. Zirconium oxide supported on boehmite nanoparticles (Pr.S‐ZrO@boehmite) was characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and inductively coupled plasma technique. The catalytic application of Pr.S‐ZrO@boehmite was studied in C–O and C–S coupling reactions for synthesis of valuable compounds such as ether and sulfide derivatives. All products were obtained in good to excellent yields and the catalyst could be recovered and reused several times without significant loss of catalytic efficiency. Furthermore, zirconium oxide is rarely used as catalyst for cross‐coupling reactions.     

MicroRNA-499a-5p Promotes Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells to Cardiomyocytes

Since the adult mammalian heart has limited regenerative capacity, cardiac trauma, disease, and aging cause permanent loss of contractile tissue. This has fueled the development of stem cell-based strategies to provide the damaged heart with new cardiomyocytes. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are capable of self-renewal and differentiation into cardiomyocytes, albeit inefficiently. MicroRNAs (miRNAs, miRs) are non-coding RNAs that have the potential to control stem cell fate decisions and are employed in cardiac regeneration and repair. In this study, we tested the hypothesis that overexpression of miR-499a induces cardiomyogenic differentiation in BM-MSCs. Human BM-MSCs (hBM-MSCs) were transduced with lentiviral vectors encoding miR-499a-3p or miR-499a-5p and analyzed by immunostaining and western blotting methods 14 days post-transduction. MiR-499a-5p-transduced cells adopted a polygonal/rod-shaped (myocyte-like) phenotype and showed an increase in the expression of the cardiomyocyte markers α-actinin and cTnI, as cardiogenic differentiation markers. These results indicate that miR-499a-5p overexpression promotes the cardiomyogenic differentiation of hBM-MSCs and may thereby increase their therapeutic efficiency in cardiac regeneration.     

Enzyme Models—From Catalysis to Prodrugs

Enzymes are highly specific biological catalysts that accelerate the rate of chemical reactions within the cell. Our knowledge of how enzymes work remains incomplete. Computational methodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play an important role in elucidating the detailed mechanisms of enzymatic reactions where experimental research measurements are not possible. Theories invoked by a variety of scientists indicate that enzymes work as structural scaffolds that serve to bring together and orient the reactants so that the reaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzyme catalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokinetics of drugs; classical prodrug approaches focus on alternating the physicochemical properties, while chemical modern approaches are based on the knowledge gained from the chemistry of enzyme models and correlations between experimental and calculated rate values of intramolecular processes (enzyme models). A large number of prodrugs have been designed and developed to improve the effectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), antiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamic acid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol), antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin. This article describes the works done on enzyme models and the computational methods used to understand enzyme catalysis and to help in the development of efficient prodrugs.     

Stereoselective Synthesis of the Di-Spirooxindole Analogs Based Oxindole and Cyclohexanone Moieties as Potential Anticancer Agents

A new series of di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were synthesized. Initially, azomethine ylides were generated via reaction of the substituted isatins 3a–f (isatin, 3a, 6-chloroisatin, 3b, 5-fluoroisatin, 3c, 5-nitroisatin, 3d, 5-methoxyisatin, 3e, and 5-methylisatin, 3f, and (2S)-octahydro-1H-indole-2-carboxylic acid 2, in situ azomethine ylides reacted with the cyclohexanone based-chalcone 1a–f to afford the target di-spirooxindole compounds 4a–n. This one-pot method provided diverse structurally complex molecules, with biologically relevant spirocycles in a good yields. All synthesized di-spirooxindole analogs, engrafted with oxindole and cyclohexanone moieties, were evaluated for their anticancer activity against four cancer cell lines, including prostate PC3, cervical HeLa, and breast (MCF-7, and MDA-MB231) cancer cell lines. The cytotoxicity of these di-spirooxindole analogs was also examined against human fibroblast BJ cell lines, and they appeared to be non-cytotoxic. Compound 4b was identified as the most active member of this series against prostate cancer cell line PC3 (IC₅₀ = 3.7 ± 1.0 µM). The cyclohexanone engrafted di-spirooxindole analogs 4a and 4l (IC₅₀ = 7.1 ± 0.2, and 7.2 ± 0.5 µM, respectively) were active against HeLa cancer cells, whereas NO₂ substituted isatin ring and meta-fluoro-substituted (2E,6E)-2,6-dibenzylidenecyclohexanone containing 4i (IC₅₀ = 7.63 ± 0.08 µM) appeared to be a promising agent against the triple negative breast cancer MDA-MB231 cell line. To explore the plausible mechanism of anticancer activity of di-spirooxindole analogs, molecular docking studies were investigated which suggested that spirooxindole analogs potentially inhibit the activity of MDM2.     

Nanomaterials for Biomedical Applications: Production,Characterisations, Recent Trends and Difficulties

Designing of nanomaterials has now become a top-priority research goal with a view to developing specific applications in the biomedical fields. In fact, the recent trends in the literature show that there is a lack of in-depth reviews that specifically highlight the current knowledge based on the design and production of nanomaterials. Considerations of size, shape, surface charge and microstructures are important factors in this regard as they affect the performance of nanoparticles (NPs). These parameters are also found to be dependent on their synthesis methods. The characterisation techniques that have been used for the investigation of these nanomaterials are relatively different in their concepts, sample preparation methods and obtained results. Consequently, this review article aims to carry out an in-depth discussion on the recent trends on nanomaterials for biomedical engineering, with a particular emphasis on the choices of the nanomaterials, preparation methods/instruments and characterisations techniques used for designing of nanomaterials. Key applications of these nanomaterials, such as tissue regeneration, medication delivery and wound healing, are also discussed briefly. Covering this knowledge gap will result in a better understanding of the role of nanomaterial design and subsequent larger-scale applications in terms of both its potential and difficulties.     

Synthesis,design, and antimicrobial activity of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinones based on quinoline derivatives

The pyrido[2,3-d]pyrimidine moieties are one of the most biologically widespread heterocyclic compounds as antimicrobial, antioxidant, antitubercular, antiviral and anti-inflammatory. Hence, we synthesized an efficient new series of 2-thioxo-pyrido[2,3-d]pyrimidinone, 2-hydrazinyl-(quinolin-2-yl)pyrido[2,3-d]pyrimidinone,N′-(quinolin-2-yl)-pyrido[2,3-d]pyrimidine-(formo/aceto)-hydrazide and substituted-(quinolin-2-yl)pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinone derivatives. The characterization of new compounds was corresponded by using spectroscopic techniques, IR, NMR and Mass spectra. In vitro, all compounds were evaluated as antimicrobial activity compared with cefotaxime sodium and nystatin as the standard drug. This work deals with the exploration of the new heterocyclic compounds and medicinal diversity of quinoline-pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives that might pave the way for long in the discovery of therapeutic medicine for future drug design.     

Enhancing the Anticancer Potential of Targeting Tumor-Associated Metalloenzymes via VEGFR Inhibition by New Triazolo[4,3-a]pyrimidinone Acyclo C-Nucleosides Multitarget Agents

The role of metalloenzymes in tumor progression had broadened their application in cancer therapy. Of these, MMPs and CAs are validated druggable targets that share some pivotal signaling pathways. The majority of MMPs or CAs inhibitors are designed as single-target agents. Despite their transient efficacy, these agents are often susceptible to resistance. This set the stage to introduce dual inhibitors of correlated MMPs and CAs. The next step is expected to target the common vital signaling nodes as well. In this regard, VEGFR-2 is central to various tumorigenesis events involving both families, especially MMP-2 and CA II. Herein, we report simultaneous inhibition of MMP-2, CA II, and VEGFR-2 via rationally designed hybrid 1,2,4-triazolo[4,3-a]pyrimidinone acyclo C-nucleosides. The promising derivatives were nanomolar inhibitors of VEGFR-2 (8; IC₅₀ = 5.89 nM, 9; IC₅₀ = 10.52 nM) and MMP-2 (8; IC₅₀ = 17.44 nM, 9; IC₅₀ = 30.93 nM) and submicromolar inhibitors of CA II (8; IC₅₀ = 0.21 µM, 9; IC₅₀ = 0.36 µM). Docking studies predicted their binding modes into the enzyme active sites and the structural determinants of activity regarding substitution and regioselectivity. MTT assay demonstrated that both compounds were 12 folds safer than doxorubicin with superior anticancer activities against three human cancers recording single-digit nanomolar IC₅₀, thus echoing their enzymatic activities. Up to our knowledge, this study introduces the first in class triazolopyrimidinone acyclo C-nucleosides VEGFR-2/MMP-2/CA II inhibitors that deserve further investigation.